Pharmacological inhibition of interleukin-1 activity on T cells by hydrocortisone, cyclosporine, prostaglandins, and cyclic nucleotides.

ABSTRACT

The effects of a panel of hormones and pharmacological agents on the activation of T cells by a combination of interleukin-1 and phytohemagglutinin (IL-1/PHA) was studied. Pharmacological effects on various stages of IL-1/PHA-induced interleukin-2 (IL-2) production by the cloned murine thymoma cell line LBRM-33-1A5.7 were dissected using a multi-step assay procedure. A 4-h lag phase in the kinetics of IL-2 production allowed the operational definition of an early, IL-1-dependent programming stage, followed by an IL-2-production stage of the assay. A cell-washing procedure between these stages was introduced in order to distinguish IL-1 receptor antagonists from functional IL-1/PHA antagonists. Hydrocortisone and cyclosporine were potent inhibitors (active in the nM range) of both stages of IL-2 production, suggesting that neither is an IL-1 receptor antagonist. The cyclic adenosine monophosphate (cAMP)-elevating agents prostaglandin E2, dibutyryl cAMP, and theophylline inhibited IL-2 production during the early, IL-1-dependent programming stage. By contrast, prostaglandin F2 alpha and dibutyryl cyclic guanosine monophosphate did not appreciably inhibit IL-1/PHA activity. These results are discussed in relationship to the effects of these test agents in thymocyte IL-1 assays or mitogenesis assays and the implications toward understanding the mechanisms underlying IL-1/PHA activation of T cells.